Regulation of gas exchange and metabolism in exercise, system limits and age-related modulation

我们的研究是在人体系统水平的综合生理学。我们研究了运动过程中气体交换、心血管反应、肌肉血流量和肌肉代谢的控制。衰老被用来说明这些系统的可塑性，老年人提供了一个模型来辨别心血管控制因素，气体交换和肌肉代谢的调节，以及运动反应的限制因素。我们研究的一个主题是我们对O2摄取（VO 2动力学）调节的时间过程的研究，它提供了关于心血管和肌肉代谢（线粒体呼吸）调节运动能量需求之间的控制机制和动态“耦合”的信息。我们的研究的一个目标是隔离控制VO 2动力学和O2输送和/或利用所施加的限制的机制。该科学方法使用逐呼吸肺泡气体交换（VO 2）结合多普勒超声逐搏动脉血流测量和近红外光谱（NIRS）局部肌肉氧合/脱氧测量;我们一直是使用这些组合技术的领导者。此外，肌肉活检和31 P-磁共振光谱用于测量肌肉基质供应，代谢物含量和酶活性的变化。我们一直发现老年人的VO 2动力学减慢，并且已经证明这是由于活动肌纤维的微血管血流（O2输送）“缓慢”所致。其他研究探索了氧化酶活化和底物提供的潜在限制。在这个授予周期中提出的目标是检查肌肉O2输送和（微）血管控制如何受到老年和年轻男性和女性运动训练的影响（即，年龄和性别差异），并继续研究老年人和青年人肌肉酶的激活和底物供应以及运动训练。这些研究有助于我们了解身体活动的能量供应控制，并为预防或逆转可能导致运动不耐受的心血管和/或代谢系统的年龄相关变化提供指导。

Our research is in integrative physiology at the systems level in humans. We examine the control of gas exchange, cardiovascular responses, muscle blood flow, and muscle metabolism during exercise. Ageing is used to illustrate the plasticity of these systems, and older adults provide a model to discern cardiovascular control factors, regulation of gas exchange and muscle metabolism, and limiting factors in the exercise response. A theme in our research is our studies of the time course of adjustment of O2 uptake (VO2 kinetics) which provides information on control mechanisms and the dynamic "coupling" between cardiovascular and muscle metabolic (mitochondrial respiration) adjustments to the energy demands of exercise. An objective of our research is to isolate mechanisms controlling VO2 kinetics and the constraints imposed by O2 delivery and/or utilization. The scientific approach uses breath-by-breath alveolar gas exchange (VO2) coupled with measures of beat-by-beat arterial blood flow by Doppler ultrasound, and near-infrared spectroscopy (NIRS) measures of local muscle oxy/deoxygenation; we have been leaders in using these combined technologies. Also, muscle biopsy and 31P-magnetic resonance spectroscopy are used to measure changes in muscle substrate provision, metabolite contents and enzyme activities. We consistently find VO2 kinetics slowed in older adults, and have shown this to be consequent to a "sluggish" microvascular blood flow (O2 delivery) to the active muscle fibres. Other studies explore potential limitations of oxidative enzyme activation and substrate provision. The objective proposed in this granting cycle is to examine how muscle O2 delivery and (micro)vascular control is influenced by exercise training in older and younger men and women (i.e., age and sex differences), and continue studies of the activation of muscle enzyme and substrate provision in old and young and with exercise training. These studies contribute to our understanding of control of energy provision for physical activity, and provide direction for preventing or reversing age-related changes to the cardiovascular and/or metabolic systems which may contribute to exercise intolerance.